Paracrine Effects of Mesenchymal Stem Cells-Conditioned Medium on Microglial Cytokines Expression and Nitric Oxide Production

The present work reports the effect of the long-term exposure bone marrow mesenchymal stem cells from chronic ischemic heart disease patients with erythropoietin on morpho-functional properties. The mesenchymal stem cells were grown under 3rd passage in medium supplemented with 33.4 IU/mL of recormon to study expression of adhesion molecules, erythropoietin receptor, cytokine receptor to common β-chain on surface, and proliferative potential (MTT test, CFU, cell cycle), migratory ability, nitric oxide production under growth factor deprivation, oxidative stress and hyperglycemia conditions, and autophagy activity, and ultrastructure changes in cells. The results showed that the long-term exposure mesenchymal stem cells with erythropoietin significantly increased proliferation, nitric oxide production and some adhesion molecules and receptors expression on surface of those cells. In addition, the erythropoietin long-term exposure with mesenchymal stem cells increases autophagy activity. The finding of this work indicates that erythropoietin could be used to augment cell resistance to adverse microenvironment condition.

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Polyamines Modulate Nitric Oxide Production andCox-2Gene Expression in Response to Mechanical Loading in Human Adipose Tissue-Derived Mesenchymal Stem Cells

Stem Cells ◽

10.1634/stemcells.2005-0625 ◽

2006 ◽

Vol 24 (10) ◽

pp. 2262-2269 ◽

Cited By ~ 37

Author(s):

Geuranne S. Tjabringa ◽

Peter S. Vezeridis ◽

Behrouz Zandieh-Doulabi ◽

Marco N. Helder ◽

Paul I.J.M. Wuisman ◽

...

Keyword(s):

Nitric Oxide ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Adipose Tissue ◽

Mechanical Loading ◽

Human Adipose Tissue ◽

Nitric Oxide Production ◽

Oxide Production

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Genetically Engineered Mesenchymal Stem Cells that Overexpress ACE2 or Angiotensin‐(1–7) Show Enhanced Nitric‐Oxide Production

The FASEB Journal ◽

10.1096/fasebj.27.1_supplement.lb689 ◽

2013 ◽

Vol 27 (S1) ◽

Author(s):

Vinayak Shenoy ◽

Meng Liu ◽

Anandharajan Rathinasabapathy ◽

Yanfei Qi ◽

Michael J Katovich ◽

...

Keyword(s):

Nitric Oxide ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Genetically Engineered ◽

Nitric Oxide Production ◽

Oxide Production

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Extracellular Vesicles from Adipose-Derived Mesenchymal Stem Cells Downregulate Senescence Features in Osteoarthritic Osteoblasts

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/7197598 ◽

2017 ◽

Vol 2017 ◽

pp. 1-12 ◽

Cited By ~ 31

Author(s):

Miguel Tofiño-Vian ◽

Maria Isabel Guillén ◽

María Dolores Pérez del Caz ◽

Miguel Angel Castejón ◽

Maria José Alcaraz

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Conditioned Medium ◽

Extracellular Vesicles ◽

Prostaglandin E ◽

Protective Effects ◽

Relevant Factor ◽

Paracrine Effects ◽

Inflammatory Stress ◽

And Oxidative Stress

Osteoarthritis (OA) affects all articular tissues leading to pain and disability. The dysregulation of bone metabolism may contribute to the progression of this condition. Adipose-derived mesenchymal stem cells (ASC) are attractive candidates in the search of novel strategies for OA treatment and exert anti-inflammatory and cytoprotective effects on cartilage. Chronic inflammation in OA is a relevant factor in the development of cellular senescence and joint degradation. In this study, we extend our previous observations of ASC paracrine effects to study the influence of conditioned medium and extracellular vesicles from ASC on senescence induced by inflammatory stress in OA osteoblasts. Our results in cells stimulated with interleukin- (IL-) 1βindicate that conditioned medium, microvesicles, and exosomes from ASC downregulate senescence-associatedβ-galactosidase activity and the accumulation ofγH2AX foci. In addition, they reduced the production of inflammatory mediators, with the highest effect on IL-6 and prostaglandin E2. The control of mitochondrial membrane alterations and oxidative stress may provide a mechanism for the protective effects of ASC in OA osteoblasts. We have also shown that microvesicles and exosomes mediate the paracrine effects of ASC. Our study suggests that correction of abnormal osteoblast metabolism by ASC products may contribute to their protective effects.

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Pre-activation of mesenchymal stem cells with TNF-α, IL-1β and nitric oxide enhances its paracrine effects on radiation-induced intestinal injury

Scientific Reports ◽

10.1038/srep08718 ◽

2015 ◽

Vol 5 (1) ◽

Cited By ~ 61

Author(s):

Hao Chen ◽

Xiao-Hui Min ◽

Qi-Yi Wang ◽

Felix W. Leung ◽

Liu Shi ◽

...

Keyword(s):

Nitric Oxide ◽

Stem Cells ◽

Mesenchymal Stem Cells ◽

Intestinal Injury ◽

Paracrine Effects ◽

Tnf Α ◽

Radiation Induced

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Paracrine effects of mesenchymal stem cells in cisplatin-induced renal injury require heme oxygenase-1

AJP Renal Physiology ◽

10.1152/ajprenal.00594.2010 ◽

2011 ◽

Vol 300 (1) ◽

pp. F254-F262 ◽

Cited By ~ 79

Author(s):

Abolfazl Zarjou ◽

Junghyun Kim ◽

Amie M. Traylor ◽

Paul W. Sanders ◽

József Balla ◽

...

Keyword(s):

Stem Cells ◽

Mesenchymal Stem Cells ◽

Growth Factor ◽

Conditioned Medium ◽

Heme Oxygenase ◽

Morphological Changes ◽

Heme Oxygenase 1 ◽

Paracrine Effects ◽

Angiogenic Potential ◽

Promising Therapeutic Approach

Multipotent mesenchymal stem cells (MSC) have become a popular and promising therapeutic approach in many clinical conditions. MSC are beneficial in animal models of acute kidney injury (AKI), by mediating differentiation-independent paracrine properties, and have prompted ongoing clinical trials to evaluate the safety and efficacy of MSC. Heme oxygenase-1 (HO-1) is induced in response to stress including AKI and has important anti-apoptotic, anti-inflammatory, and proangiogenic properties in these settings. We therefore examined whether HO-1 plays a role in the beneficial effects of MSC in AKI. We isolated MSC from bone marrow of age-matched HO-1+/+ and HO-1−/− mice. Our studies indicate that while differentiation of MSC into osteo- and adipocytic lineages did not differ between cells isolated from HO-1+/+ and HO-1−/− mice, MSC from HO-1−/− mice had significantly lower angiogenic potential. Moreover, HO-1−/− MSC demonstrated reduced expression and secretion of several important growth and proangiogenic factors (stromal cell-derived factor-1, vascular endothelial growth factor-A, and hepatocyte growth factor) compared with MSC derived from HO-1+/+ mice. In addition, conditioned medium of HO-1+/+ MSC rescued functional and morphological changes associated with cisplatin-induced AKI, while the HO-1−/−-conditioned medium was ineffectual. Our studies indicate that HO-1 plays an important role in MSC-mediated protection. The results expand understanding of the renoprotective effects of MSC and may provide novel strategies to better utilize MSC in various disease models.

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